Abstract: There are stark disparities in perinatal outcomes between Black and non-Black women in the United States. Even when controlling for socioeconomic status and medical comorbidities, Black women have a higher rate of cesarean delivery, severe maternal morbidity (SMM) and overall maternal mortality (MM). In fact, Black women die at three times the rate of white women during and following pregnancy. While racial disparities in perinatal outcomes are multifactorial, there is increasing evidence that environmental exposures?poverty, psychosocial factors, maternal adverse childhood experiences (ACE) and stress confer significant health risk. For example, higher ACE scores have been linked to a host of negative physical and psychosocial outcomes outside of pregnancy such as increased risk for cardiovascular disease, diabetes, cancers, and depression. Similarly, higher ACE scores and higher stress have also been associated with adverse pregnancy outcomes. Despite these findings, the biological underpinnings as to how early life experiences and maternal stress may lead to MM and SMM remain a mystery. Our proposal will provide an integrated and innovative approach to understand biological, specifically immunological, and sociocultural factors that contribute to SMM. It is understood that the factors and causes leading to SMM and MM are multifaceted. Yet, research in non-obstetrical populations have revealed important findings. First, perturbations in immune function are key biological events contributing to disease states such as diabetes, hypertension and adverse vascular phenotypes. Second, psychosocial stressors, specifically early life stressors, contribute to adverse health outcomes and are implicated in observed racial disparities. There are large knowledge gaps as to how psychosocial stressors may contribute to maternal morbidity and to the significant increases in maternal morbidity and mortality among black women. We hypothesize that psychosocial stressors alter the functional immune profile in pregnant women leading to diverse biological effects that predispose women to SMM and MM. In our recently funded renewal RO1, we are enrolling 800 pregnant women or 200 per year. Inclusion criteria for this study includes women to be self-reporting race as black. We are already obtaining psychosocial metrics, such as adverse childhood events (ACE), perceived stress (PSS) and neighborhood deprivation. For the period of this supplement, we propose to enroll 120 pregnant women, from the 200 expected in the parent R01 in year 1, to participate in a sub-study to determine how maternal stress may perturb immune function. We will assess functional immune profiles between 20-26 weeks to reflect a period prior to most maternal morbidity events. We will compare the immune profile between black women who have high and low scores on the psychosocial metrics as our primary outcome. As secondary outcome will be exploratory and will investigate the association of a functional immune profile with maternal morbidity and severe maternal morbidity in these 120 women. Medical records for all 120 patients will be carefully adjudicated for SMM and MM.